Going viral: First-year students get hands-on experience in phage genomics course

There is a long list of learning objectives for the HON 150/155 phage genomics course, in which first-year undergraduates conduct hands-on research.

They learn how to purify and isolate novel bacteriophages — viruses that infect bacterial hosts — from soil samples.

The students learn how to characterize their individual phages — which have the miniscule diameter of around 65 nanometers and can only be viewed using an electron microscope. They learn essential laboratory techniques including microscopy, aseptic methods and comparative genomic analysis.

They learn how to analyze data and design unique experiments. And they learn to read and think like scientists.

But most importantly, the first-year UMaine students learn how to learn. Because without that knowledge, the rest is moot.

“It is not a sink or swim situation,” says Sally Molloy, assistant professor of genomics and co-instructor of the course. “We teach students how to learn so they can function in any learning situation in the future, whether that is in STEM fields or the humanities.”

The yearlong course is sponsored by the Howard Hughes Medical Institute (HHMI) and is part of a nationwide program called the Science Education Alliance (SEA) Phage Hunters Advancing Genomics and Evolutionary Science (PHAGES) research course.

The program, which started in 2008, now involves 70 campuses and 4,800 undergraduate researchers. To date, Molloy estimates that 100 UMaine students have completed the program.

The microscopic phages that the students isolate resemble tiny lunar landers and attack bacterial hosts in the family Mycobacterium smegmatis, which are nonpathogenic organisms that are found in soil, water and plants.

Keith Hutchison, professor emeritus in the Department of Molecular and Biomedical Sciences, has been teaching the course since its inception five years ago.

“Before we had our first students, I went to a national meeting and I was listening to these students who had just completed their first year presenting their work, and I remember thinking, ‘I wish my graduate students could talk this well,’” says Hutchison.

He’s now amazed when he listens to the first-year students in his own classroom.

“Many institutions don’t even have laboratories, let alone a laboratory like this. Often, before the students even get a job, they have to go on to get a master’s or a job working in a lab in order to get into graduate school,” says Hutchison.

“Our students are prepared for that by the time they walk out of the classroom at the end of their first year.”

The course is a joint effort between the Honors College and the Department of Molecular and Biomedical Sciences (MBMS). The course is now required for all incoming and transfer students within MBMS.

Students in the classroom try to figure out how their isolated virus is related to many of the other viruses that have been isolated across the United States through HHMI’s program.

The procedures students learn to analyze phages closely resemble those used to understand more complex genomes, such as the human genome. By comparing their phage with others that infect the same host, students develop an understanding of the evolution of genomes.

Bacteriophages are considered the most numerous biological entity on Earth. For every bacterium, scientists estimate there are approximately 10 phages that can attack it.

This makes the phage an incredibly effective educational tool because the amount of scientific discovery available to students is seemingly endless, explains Molloy. Because every phage that is isolated is going to be different than any other phage that has been isolated before.

“Incorporating fundamental research in the classroom is one way to motivate students to become more autonomous learners,” says Molloy. “Students cultivate an intrinsic curiosity that promotes independent learning and a desire for more research opportunities outside of the classroom.”

During the first semester of the course, students also have the opportunity to use a transmission electron microscope (TEM), which provides nanometer scale images of their phages to be used for analysis.

Having access and training on an electron microscope during a student’s first year is almost unheard of, says Kelly Edwards, lab technician for the Electron Microscopy Laboratory in Murray Hall.

“To my knowledge, this is currently the only lab in the state that allows people from outside the university to come in and use the facilities,” says Edwards, who has worked at UMaine since 1980.

The TEM allows students to see their virus with their own eyes, which Edwards says is the real thrill. The lab also provides training in light and electron microscopy to faculty, staff, graduate students and members of the community.

“The students know something is creating the things they are seeing. They may have some kind of picture in their mind of what this thing looks like. But when you put it in the TEM you actually see the creature that you have isolated and grown up and purified. It’s really exciting for the students,” says Edwards.

The information that students gather from the TEM helps them classify what type of virus they have isolated, which goes into HHMI’s national database.

“It’s a big deal,” says Edwards.

At the end of the first semester, UMaine students select one DNA sample from the isolated phages to get sequenced, which provides the precise order of nucleotides within a DNA molecule. Only one sample is chosen because the process cost around $1,500, which is covered by HHMI.

When students return for the spring semester, they conduct independent research projects using computer-based analyses to understand the biology of their individual phages and the structure of its genome.

At the end of the year, students make a similar decision about who will represent the class at the national meeting at HHMI headquarters in Virginia.

Ethan Thibault, a double major in microbiology and molecular and cellular biology and a part of the Honors College, was one of two students selected last spring to present at the national phage conference in Virginia.

“Not only did we get to perform research beyond most freshmen experiences, we gained practice writing manuscripts, and reading and analyzing scientific journal articles,” says Thibault, who plans to pursue graduate school after he graduates in May 2018.

“I learned how to take information, formulate an experiment based on that, analyze the results and then figure out where to go next,” he says.

“I learned how to be a researcher and skills that will help me for the rest of my scientific career.”

Because of those skills, Thibault was accepted to a National Science Foundation Research Experience of Undergraduates, which included a paid internship at South Dakota State University working with salinity tolerance of prairie cordgrass.

“UMaine has pushed me to strive for excellence and has allowed me to pursue research that I never expected I would have the opportunity to do as a first-year student,” says Thibault.

“Keith and Sally are two absolutely amazing professors. Sally always has the students well-being in mind. She will do anything to help you succeed. You will not meet another professor as devoted to her students as her,” says Thibault.

Max Dorman agrees.

Dorman is a molecular and cellular biology major and is a part of the Honors College. Dorman also presented his research at HHMI’s national meeting in 2015, alongside Thibault.

“To me, the phage course was what every course should be like,” says Dorman. “There was full-group discussion; there was debate; there was learning; there were experiments.”

A life-changing skill that Dorman learned in the course was how to develop a growth mindset. In order to do so, explains Dorman, you must “embrace failure as a part of the learning process.”

It’s a skill that Molloy hopes all her students leave her course with.

Because in science, the answer is not always apparent.

“That’s the biggest part of this course — teaching students how to learn, how to apply information to new problems, and to tackle things that would at first seem impossible,” says Molloy.

“Being in a classroom where students are making discoveries and you are learning through them, I don’t think I’d like to teach in any other way again.”

Contact: Margaret Nagle, 581.3745